Integrating Correctional and Community Health Care: An Innovative Approach for Clinical Learning in a Baccalaureate Nursing Program.
With an evolving focus on primary, community-based, and patient-centered care rather than acute, hospital-centric, disease-focused care, and recognition of the importance of coordinating care and managing transitions across providers and settings of care, registered nurses need to be prepared from a different and broader knowledge base and skills set. A culture change among nurse educators and administrators and in nursing education is needed to prepare competent registered nurses capable of practicing from a health promotion, disease prevention, community- and population-focused construct in caring for a population of patients who are presenting health problems and conditions that persist across decades and/or lifetimes. While healthcare delivery is moving from the hospital to ambulatory and community settings, community-based educational opportunities for nursing students are shrinking due to a variety of reasons, including but not limited to increased regulatory requirements, the presence of competing numbers of nursing schools and their increased enrollment of students, and decreasing availability of community resources capable and willing to precept students in an all-day interactive learning environment. A detailed discussion of one college of nursings' journey to find an innovative solution and approach to the dilemma of limited and decreasing available community clinical sites to prepare senior level prelicensure baccalaureate nursing students for healthcare practice in the twenty-first century. This article demonstrated how medium/maximum prisons can provide an ideal learning experience for not only technical nursing skills but more importantly for reinforcing key learning goals for community-based care, raising population-based awareness, and promoting cultural awareness and sensitivity. In addition, this college of nursing overcame the challenges of initiating and maintaining clinical placement in a prison facility, collaboratively developed strategies to insure student and faculty safety satisfying legal and administrative concerns for both the college of nursing and the prison, and developed educational postclinical assignments that solidified clinical course and nursing program objectives. Lastly, this college of nursing quickly learned that not only did nursing students agree to clinical placement in an all-male medium- to maximum-security prison despite its accompanying restrictive regulations especially as it relates to their access to personal technology devices, but there was an unknown desire for a unique clinical experience. The initial pilot program of placing eight senior level prelicensure baccalaureate nursing students in a 4,000-person all male medium- to maximum-security prison for their community clinical rotation has expanded to include three state-run maximum all male prisons in two states, a 3,000-person male/female federal prison, and several juvenile detention centers. Clinical placement of students in these sites is by request only, resulting in lengthy student waiting lists. This innovative approach to clinical learning has piqued the interest of graduate nurse practitioner (NP) students as well. One MSN, NP student has been placed in the federal prison every semester for over a year. Due to increasing interest from graduate students to learn correctional health nursing, the college of nursing is now expanding NP placement to the other contracted maximum-security prisons. This entire experience has changed clinical policies within a well-established academic culture and promoted creative thinking regarding how and where to clinically educate and prepare registered baccalaureate nurses for the new culture of health and wellness.


Mental contrasting of a negative future facilitates COVID-19 preventative behaviors: two randomized controlled trials.
Objective: The present research examined whether mentally contrasting a negative, feared future (i.e., infection with the Coronavirus) with a still positive reality can promote preventative actions in the context of the pandemic. Design: In two randomized controlled trials, we varied participants' mode of thought (mental contrasting of a negative future with a positive reality versus fantasizing of a negative future). Study 2 took into account the interpersonal nature of the pandemic and manipulated the mode of thought in a vicarious manner (vicarious mental contrasting versus vicarious negative fantasizing). Main Outcome Measures: After the manipulation, we assessed participants' intentions to learn about COVID-19 (Study 1) and attention to COVID-19 information (Study 1 and 2). Three days later, we measured the amount of physical distancing (Study 1 and 2). Results: Study 1 found that mental contrasting leads to more COVID-19 preventative behaviors than mere negative fantasizing. In Study 2, we observed that vicarious mental contrasting facilitates physical distancing among people who initially showed low compliance with COVID-19 preventative behaviors and thus were in most need of a boost in preventative behavior. Conclusion: The findings suggest that mental contrasting of negative fantasies may be an effective way to encourage COVID-19 preventative behaviors.


Do nutrition labels improve dietary outcomes?
The disclosure of nutritional characteristics of most packaged foods became mandatory in the United States with the implementation of the Nutrition Labeling and Education Act (NLEA) in 1994. Under the NLEA regulations, a 'Nutrition Facts' panel displays information on nutrients such as calories, total and saturated fats, cholesterol, and sodium in a standardized format. By providing nutrition information in a credible, distinctive, and easy-to-read format, the new label was expected to help consumers choose healthier, more nutritious diets. This paper examines whether the disclosure of nutrition information through the mandatory labels impacted consumer diets. Assessing the dietary effects of labeling is problematic due to the confounding of the label effect with unobserved label user characteristics. This self-selection problem is addressed by exploiting the fact that the NLEA exempts away-from-home foods from mandatory labeling. Difference-in-differences models that account for zero away-from-home intakes suggest that the labels increase fiber and iron intakes of label users compared with label nonusers. In comparison, a model that does not account for self-selection implies significant label effects for all but two of the 13 nutrients that are listed on the label.


Chorismate synthase from Staphylococcus aureus.
The aroC gene encoding chorismate synthase and the ndk gene encoding nucleoside diphosphate kinase (Ndk) were cloned from Staphylococcus aureus. DNA sequencing suggests that aroC is located in an operon with aroB and aroA and encodes a protein of 388 amino acids with 61% identity to the aroF gene product of Bacillus subtilis. The ndk gene of S. aureus encodes a protein of 149 amino acids which exhibits a high degree of identity to other bacterial Ndk proteins. The 3' end of the S. aureus gerCC gene was also identified by sequencing and was located immediately upstream of ndk. The gerCA and gerCB genes were found to be located upstream of gerCC by Southern hybridization analysis. This observed linkage of the gerC genes with the ndk, aroC and aroB genes has been similarly observed in B. subtilis. The S. aureus chorismate synthase was overexpressed to a high level in Escherichia coli using a T7 promoter plasmid construct, the enzyme was purified to near homogeneity in two steps and found to be a homotetramer with a subunit molecular mass, estimated by electrospray mass spectrometry, of 43024 Da. The properties of S. aureus chorismate synthase are compared with those of the B. subtilis and E. coli enzymes.


SCALING OF APPARENT VISCOSITY.
Observers made numerical judgments of the apparent viscosities of silicone liquids whose absolute viscosities ranged from 10.3 to 95,000 centipoises. Judgments were made by three procedures: shaking or turning a bottle containing the liquid, stirring the liquid with a rod with the eyes blindfolded, and stirring with the eyes open. For all these methods of judging, apparent viscosity was found to grow as the absolute viscosity raised to a fractional power. The exponents ranged from 0.42 to 0.46. The perception of viscosity follows the psychophysical power law that seems to govern prothetic perceptual continua.


Pear genetics: Recent advances, new prospects, and a roadmap for the future.
Pear, belonging to the genus Pyrus, is one of the most economically important temperate fruit crops. Pyrus is an important genus of the Rosaceae family, subfamily Maloideae, and has at least 22 different species with over 5000 accessions maintained or identified worldwide. With the release of draft whole-genome sequences for Pyrus, opportunities for pursuing studies on the evolution, domestication, and molecular breeding of pear, as well as for conducting comparative genomics analyses within the Rosaceae family, have been greatly expanded. In this review, we highlight key advances in pear genetics, genomics, and breeding driven by the availability of whole-genome sequences, including whole-genome resequencing efforts, pear domestication, and evolution. We cover updates on new resources for undertaking gene identification and molecular breeding, as well as for pursuing functional validation of genes associated with desirable economic traits. We also explore future directions for "pear-omics".


Hungry to gamble? Ghrelin as a predictor of persistent gambling in the face of loss.
Ghrelin, a peptide hormone associated with appetite, is also linked to increased reward seeking behaviors, including food, sex, and drug seeking behaviors through the stimulation of the mesolimbic dopaminergic system. Moreover, plasma ghrelin concentrations are increased by cues that predict rewards, suggesting that cues could facilitate cravings and ultimately relapse. In this project we examined the effects of an overnight fast, a manipulation known to increase ghrelin concentrations, on gambling behaviors. We also examined if cues associated with gambling would also increase ghrelin and, if so, we examined if these increases were associated with gambling behavior. One hundred and one (37 females) participants were asked to fast overnight or after breakfast and then asked to complete food and gambling craving questionnaires. Participants were then presented with gambling cues (a casino like environment in the lab) or a control cue (a cubicle with a computer). After the cue, subjects filled gambling craving questionnaires, and were allowed to gamble. Following 25 practice spins, the slot machines were fixed so that all subsequent spins were losses, and the number of spins in spite of losses were quantified. Blood samples were collected throughout the experiment. Results showed that the gambling cues significantly increased ghrelin concentrations particularly in fasted individuals, and that ghrelin concentrations 20 min after the cue were the best predictor for gambling persistence in the face of continued loss (p < 0.05). Our results suggest that cues that predict the opportunity to gamble have an acute effect on ghrelin concentrations that is facilitated by fasting, and that ghrelin concentrations are a significant predictor of gambling persistence.


Procedures: do we really want to know them? An examination of the effects of procedural justice on self-esteem.
This study examined the effects of procedural justice on state-dependent self-esteem using the group-value model and attribution theory to present competing theoretical perspectives. The group-value model predicts a positive relationship between self-esteem and fair procedures. In contrast, attribution theory suggests procedural fairness interacts with outcome favorability to influence self-esteem. Thus, fair procedures will result in higher self-esteem ratings than unfair procedures when the outcome is positive but will result in lower self-esteem ratings than unfair procedures when the outcome is negative. The results of a laboratory and field study provide converging evidence to support the attribution theory predictions. The results of a 2nd laboratory study suggest that self-esteem is influenced by outcome expectancies, not actual outcomes.


[Organ-preserving surgery in patients with diffuse fibro-cavernous tuberculosis of the lungs].
Diffuse fibro-cavernous tuberculosis was managed in 44 patients by interventions on the cavern, the bronchi draining it, and the thoracic wall. It is shown that these operations are combined and are organ-preserving in character. The choice of the type of the operation is determined by the character of the affection of the bronchi and the activity of the tuberculous inflammation in the wall of the cavern. The use of modern technical measures (laser, ultrasonics, hemosorption) is promising.


Community participation as an interactive learning process: experiences from a schistosomiasis control project in Zimbabwe.
A schistosomiasis control project was undertaken from 1994 to 1998 in Guruve District, Zimbabwe, based on the active involvement of local communities in the growing and application of the molluscicidal plant Phytolacca dodecandra as a supplement to other control measures such as chemotherapy and health education. The berries of P. dodecandra are highly molluscicidal to the intermediate host snails of schistosomiasis and is rapidly degradable in water. It was observed that plant care fluctuated during the study period. Only a few households participated in snail control activities, although 97% of respondents in a baseline survey had stated a willingness to take part. This invoked an investigation to explore the reality from a user perspective. Focus group discussions, semi-structured interviews and observations were used to solicit information. In spite of a cultural inclination for collective work, many reasons for low-level involvement emerged, inter alia the low perceived value of the project, demands for tangible benefits, inaccessible fields and weak leadership. This study shows that community participation is a complex process upon which a multiplicity of social and cultural determinants have an impact. If community participation is to become successful in development programmes it ought to be viewed as a mutual learning process where obstacles are identified and discussed and solutions shared among community members and project staff.


Abnormal Ventricular and Aortic Wall Properties Can Cause Inconsistencies in Grading Aortic Regurgitation Severity: A Computer Simulation Study.
Assessment of aortic regurgitation (AR) severity is often based on Doppler echocardiographic imaging. Hemodynamic responses to AR are influenced by the interplay among cardiovascular properties, including left ventricular (LV) and aortic tissue properties, that cannot be measured directly. The aim of this study was to investigate how both echocardiographic measures of AR severity and the hemodynamic consequences of AR are influenced by LV and aortic stiffness. AR was simulated using the CircAdapt computational model of the human cardiovascular system. Simulations were performed with normal LV and aortic stiffness, high LV stiffness, high aortic stiffness, and high LV and aortic stiffness. For each configuration of levels of stiffness, four AR severity grades were simulated by setting the effective regurgitant orifice area (ROA) of the aortic valve at 0, 0.05, 0.25, and 0.6 cm2, representing no, mild, moderate, and severe AR, respectively. The regurgitant volume, regurgitant fraction (RF), and pressure half-time (PHT) were computed for each simulation giving an AR severity score (mild, moderate, or severe). Mean left atrial pressure was also calculated. Increasing ROA resulted in faster decay of diastolic flow velocity and larger regurgitant blood flow across the aortic valve. This caused shorter PHT and larger regurgitant volume and RF, all indicating higher AR severity. Increasing aortic stiffness resulted in a larger decline in diastolic aortic pressure, whereas increasing LV stiffness resulted in a larger rise in diastolic LV pressure. Hence, increasing LV and/or aortic stiffness led to faster decay of the transvalvular pressure gradient and, therefore, to faster decay of diastolic flow velocity across the aortic valve compared with normal stiffness with the same ROA. This faster decay led, on one hand, to a shorter PHT, indicating higher severity scores, and, on the other hand, to a lower RF, as less regurgitant blood volume traveled into the left ventricle, indicating lower severity scores. AR severity scores reflected mean left atrial pressure poorly when variations in tissue properties were present. Simulating altered AR hemodynamics caused by variations in cardiovascular tissue properties led to inconsistent severity scores when evaluating the severity using RF, regurgitant volume, and PHT. In this situation, pulmonary congestion is poorly reflected by AR severity as quantified by ROA, RF, and PHT. Cardiac and aortic tissue properties should therefore be taken into account to improve clinical assessment of AR severity.


Teleosts as Model Organisms To Understand Host-Microbe Interactions.
Host-microbe interactions are influenced by complex host genetics and environment. Studies across animal taxa have aided our understanding of how intestinal microbiota influence vertebrate development, disease, and physiology. However, traditional mammalian studies can be limited by the use of isogenic strains, husbandry constraints that result in small sample sizes and limited statistical power, reliance on indirect characterization of gut microbial communities from fecal samples, and concerns of whether observations in artificial conditions are actually reflective of what occurs in the wild. Fish models are able to overcome many of these limitations. The extensive variation in the physiology, ecology, and natural history of fish enriches studies of the evolution and ecology of host-microbe interactions. They share physiological and immunological features common among vertebrates, including humans, and harbor complex gut microbiota, which allows identification of the mechanisms driving microbial community assembly. Their accelerated life cycles and large clutch sizes and the ease of sampling both internal and external microbial communities make them particularly well suited for robust statistical studies of microbial diversity. Gnotobiotic techniques, genetic manipulation of the microbiota and host, and transparent juveniles enable novel insights into mechanisms underlying development of the digestive tract and disease states. Many diseases involve a complex combination of genes which are difficult to manipulate in homogeneous model organisms. By taking advantage of the natural genetic variation found in wild fish populations, as well as of the availability of powerful genetic tools, future studies should be able to identify conserved genes and pathways that contribute to human genetic diseases characterized by dysbiosis.


Soy Isoflavones Promote Radioprotection of Normal Lung Tissue by Inhibition of Radiation-Induced Activation of Macrophages and Neutrophils.
Radiation therapy for lung cancer is limited by toxicity to normal lung tissue that results from an inflammatory process, leading to pneumonitis and fibrosis. Soy isoflavones mitigate inflammatory infiltrates and radiation-induced lung injury, but the cellular immune mediators involved in the radioprotective effect are unknown. Mice received a single dose of 10 Gy radiation delivered to the lungs and daily oral treatment of soy isoflavones. At different time points, mice were either processed to harvest bronchoalveolar lavage fluid for differential cell counting and lungs for flow cytometry or immunohistochemistry studies. Combined soy and radiation led to a reduction in infiltration and activation of alveolar macrophages and neutrophils in both the bronchoalveolar and lung parenchyma compartments. Soy treatment protected F4/80CD11c interstitial macrophages, which are known to play an immunoregulatory role and are decreased by radiation. Furthermore, soy isoflavones reduced the levels of nitric oxide synthase 2 expression while increasing arginase-1 expression after radiation, suggesting a switch from proinflammatory M1 macrophage to an anti-inflammatory M2 macrophage phenotype. Soy also prevented the influx of activated neutrophils in lung caused by radiation. Soy isoflavones inhibit the infiltration and activation of macrophages and neutrophils induced by radiation in lungs. Soy isoflavones-mediated modulation of macrophage and neutrophil responses to radiation may contribute to a mechanism of resolution of radiation-induced chronic inflammation leading to radioprotection of lung tissue.


Demographic and Psychographic Factors of Social Isolation During the COVID-19 Pandemic: The Importance of Technology Confidence.
The COVID-19 pandemic presents an unprecedented situation in which physical distancing and "stay at home" orders have increased the pressures for social isolation. Critically, certain demographic factors have been linked to increased feelings of isolation and loneliness. These at-risk groups for social isolation may be disproportionately affected by the changes and restrictions that have been implemented to prevent viral spread. In our analysis, we sought to evaluate if perceived feelings of social isolation, during the COVID-19 pandemic, was related to demographic and technology-related psychographic characteristics. Older adults across Canada were surveyed about their demographic background, their feelings concerning confidence and proficiency in technology use, and how frequently they have felt isolated during the pandemic. In total 927 responses from Canadians over 65 years old, of varying demographic characteristics were collected. Our data shows that many older adults are feeling isolated "Often" or "Some of the time" in 2020, regardless of most demographic factors that have been previously associated with increased isolation risk. However, feelings of proficiency in using technology was an important factor affecting feelings of isolation. Given that technology proficiency is a modifiable factor, and remained significant after adjustment for demographic factors, future efforts to reduce social isolation should consider training programs for older adults to improve technology confidence, especially in an increasingly digital world.


[Relationship between mononuclear infiltration of the epidermis and its hyperplasia after auto- and allotransplantation of the full-thickness skin of mice].
Histological and histochemical studies of the back skin were carried out with morphometry on the 1st, 2nd, 3rd, 6th, and 9th days after auto- or allotransplantation of its full thickness graft in 60 lineal (C3H) and random-bred mice. In both kinds of transplantation, mononuclear infiltration of the epidermis of the graft and the surrounding skin was established. A correlation between the intensity of this infiltration and the thickness of the epidermis in the skin surrounding the grafts and in the autograft was established. In allotransplantation, there was no such correlation in the graft. No mononuclear cells were found in regeneration layers of the epidermis. It is suggested that epidermis regeneration is stimulated by autogenous lymphocytes.


On the asymptotic behaviour of the pseudolikelihood ratio test statistic with boundary problems.
This paper considers the asymptotic distribution of the likelihood ratio statistic T for testing a subset of parameter of interest θ, θ = (γ, η), H(0) : γ = γ(0), based on the pseudolikelihood L(θ, ϕ̂), where ϕ̂ is a consistent estimator of ϕ, the nuisance parameter. We show that the asymptotic distribution of T under H(0) is a weighted sum of independent chi-squared variables. Some sufficient conditions are provided for the limiting distribution to be a chi-squared variable. When the true value of the parameter of interest, θ(0), or the true value of the nuisance parameter, ϕ(0), lies on the boundary of parameter space, the problem is shown to be asymptotically equivalent to the problem of testing the restricted mean of a multivariate normal distribution based on one observation from a multivariate normal distribution with misspecified covariance matrix, or from a mixture of multivariate normal distributions. A variety of examples are provided for which the limiting distributions of T may be mixtures of chi-squared variables. We conducted simulation studies to examine the performance of the likelihood ratio test statistics in variance component models and teratological experiments.


Foundations of children's numerical and mathematical skills: the roles of symbolic and nonsymbolic representations of numerical magnitude.
Numerical and mathematical skills are critical predictors of academic success. The last three decades have seen a substantial growth in our understanding of how the human mind and brain represent and process numbers. In particular, research has shown that we share with animals the ability to represent numerical magnitude (the total number of items in a set) and that preverbal infants can process numerical magnitude. Further research has shown that similar processing signatures characterize numerical magnitude processing across species and developmental time. These findings suggest that an approximate system for nonsymbolic (e.g., dot arrays) numerical magnitude representation serves as the basis for the acquisition of cultural, symbolic (e.g., Arabic numerals) representations of numerical magnitude. This chapter explores this hypothesis by reviewing studies that have examined the relation between individual differences in nonsymbolic numerical magnitude processing and symbolic math abilities (e.g., arithmetic). Furthermore, we examine the extent to which the available literature provides strong evidence for a link between symbolic and nonsymbolic representations of numerical magnitude at the behavioral and neural levels of analysis. We conclude that claims that symbolic number abilities are grounded in the approximate system for the nonsymbolic representation of numerical magnitude are not strongly supported by the available evidence. Alternative models and future research directions are discussed.


A Mobile Health Intervention for Adolescents Exposed to Secondhand Smoke: Pilot Feasibility and Efficacy Study.
Secondhand smoke (SHS) exposure in children and adolescents has adverse health effects. For adolescents of lower socioeconomic status (SES), exposure is widespread, evidenced in the measurement of urinary cotinine, a major metabolite of nicotine. Direct intervention with exposed children has been proposed as a novel method, yet there is minimal evidence of its efficacy. Combining this approach with a mobile health (mHealth) intervention may be more time and cost-effective and feasible for adolescent populations. In this pilot study, we assessed the feasibility and preliminary evidence of efficacy of a 30-day text message-based mHealth intervention targeted at reducing SHS exposure in adolescent populations of low SES. For the study, 14 nonsmoking and nonvaping participants between the ages of 12-21 years exposed to SHS were enrolled. The intervention consisted of a daily text message sent to the participants over the course of a month. Text message types included facts and information about SHS, behavioral methods for SHS avoidance, or true-or-false questions. Participants were asked to respond to each message within 24 hours as confirmation of receipt. Feasibility outcomes included completion of the 30-day intervention, receiving and responding to text messages, and feedback on the messages. Efficacy outcomes included a reduction in urinary cotinine, accuracy of true-or-false responses, and participants' perceptions of effectiveness. Of the 14 participants that were enrolled, 13 completed the intervention. Though not required, all participants had their own cell phones with unlimited text messaging plans. Of the total number of text messages sent to the 13 completers, 91% (372/407) of them received on-time responses. Participant feedback was generally positive, with most requesting more informational and true-or-false questions. In terms of efficacy, 54% (6/11) of participants reduced their cotinine levels (however, change for the group overall was not statistically significant (P=.33) and 45% (5/11) of participants increased their cotinine levels. Of the total number of true-or-false questions sent across all completers, 77% (56/73) were answered correctly. Participants' ratings of message effectiveness averaged 85 on a scale of 100. In this pilot study, the intervention was feasible as the majority of participants had access to a cell phone, completed the study, and engaged by responding to the messages. The efficacy of the study requires further replication, as only half of the participants reduced their cotinine levels. However, participants answered the majority of true-or-false questions accurately and reported that the messages were helpful.


Water and electrolyte transport in Henle's loop and distal tubule after renal sympathectomy in the rat.
The effect of acute renal denervation (AD) on transtubular movement of water and electrolytes in Henle's loop (LH) and distal tubule (DT) of superficial nephrons was studied by the technique of in vivo microperfusion in Inactin-anesthetized hydropenic male rats. In time-control experiments (n = 6) no changes in either whole kidney or single nephron function were detected. Predenervation results of denervation experiments (n = 10) were similar to those of the time-control series. AD resulted in increased urine, sodium, and potassium excretion in the absence of changes of either arterial blood pressure or GFR. Compared with predenervation data, AD led to significant decreases in net transtubular fluxes (J) of water and sodium in both perfused segments with delivery kept constant (delta JNa: LH = 144 +/- 26 peq X min-1, 9.1 +/- 0.3%; DT = 94 +/- 11 peq X min-1, 22.3 +/- 1.1%). Potassium absorption in the loop decreased but an increase in net addition (secretion) of K in the distal tubule on denervation occurred (delta JK = 8.7 +/- 1.9 peq X min-1, 68.7 +/- 3.2%). Use of the reperfusion technique gave similar results. These results indicate that efferent renal sympathetic nerve activity directly influences water, sodium, and potassium transport in the loop of Henle and distal tubule of the anesthetized rat.


Effects of non-toxic zinc exposure on human epidermal keratinocytes.
Zinc is an essential microelement; its importance to the skin is highlighted by the severe skin symptoms in hereditary or acquired zinc deficiency, by the improvement of several skin conditions using systemic or topical zinc preparations and by the induced intracellular zinc release upon UVB exposure, which is the main harmful environmental factor to the skin. Understanding the molecular background of the role of zinc in skin may help gain insight into the pathology of skin disorders and provide evidence for the therapeutic usefulness of zinc supplementation. Herein, we studied the effects of zinc chloride (ZnCl2) exposure on the function of HaCaT keratinocytes, and the results showed that a non-toxic elevation in the concentration of extracellular zinc (100 μM) facilitated cell proliferation and induced significant alterations in the mRNA expression of NOTCH1, IL8, and cyclooxygenase-2. In addition, increased heme oxygenase-1 (HMOX1) expression and non-toxic generation of superoxide were detected in the first 4 h. Regarding the effects on the UVB-induced toxicity, although the level of cyclobutane pyrimidine dimers in the keratinocytes pre-treated with zinc for 24 h was reduced 3 h after UVB irradiation, significantly enhanced superoxide generation was observed 10 h after UVB exposure in the zinc pre-exposed cells. The overall survival was unaffected; however, there was a decrease in the percentage of early apoptotic cells and an increase in the percentage of late apoptotic plus necrotic cells. These results suggest that the exposure of human keratinocytes to non-toxic concentrations of ZnCl2 impacts gene expression, cell proliferation and the responses to environmental stress in the skin. It would be important to further examine the role of zinc in skin and further clarify whether this issue can affect our thinking regarding the pathogenesis of skin diseases.


A critique of Paulo Freire's perspective on human nature to inform the construction of theoretical underpinnings for research.
This article presents a critique of Paulo Freire's philosophical perspective on human nature in the context of a doctoral research study to explore "muchness" or nurses' subjective experience of well-being; and demonstrates how this critique has informed the refinement of the theoretical principles used to inform research methodology and methods. Engaging in philosophical groundwork is essential for research coherence and integrity. Through this groundwork, largely informed by Freire's critical pedagogy and his ideas on humanization, I recognized the need to clarify my understanding of the concepts of persons and personhood and how this related to Freire's use of the term human beings. This clarification process is essential to ensure congruence between the theoretical principles that I draw from his work and my beliefs about persons, personhood and person-centredness. The article begins with a brief introduction to the research, followed by an overview of Freire's philosophical perspectives, and subsequently, the critique process is presented and discussed. This process involved engaging with the vast literature and debates about what it means to be a person, to make sense of the often complex and contradictory arguments. Eventually, three headings emerged that helped me to frame my evolving understanding: Our species: human beings; The kind that we are: human nature; and This person that I am: personhood. Through this process of exploration, I recognized that Freire's perspective on human nature (a) foregrounded cognitive rationality, which presented itself as a limitation when considering my ontological beliefs and the focus of my research, leading me to draw on the work of Mark Johnson and his ideas about embodiment to help me to further develop my theoretical principles; (b) focused on the "collective" rather than individuals, which is a shortcoming in relation to person-centred research that acknowledges the uniqueness of participants.


A mixed-methods analysis of patient reviews of hospital care in England: implications for public reporting of health care quality data in the United States.
In the United States patients have limited opportunities to read and write narrative reviews about hospitals. In contrast, the National Health Service (NHS) in England encourages patients to provide feedback to hospitals on their quality-reporting website, NHS Choices. The scope and content of the narrative feedback was studied. All NHS hospitals with more than 10 reviews posted on NHS Choices were included in a cross-sectional mixed-methods (qualitative and quantitative) analysis of patients' reviews of 20 randomly selected hospitals. The final sample consisted of 264 hospitals and 2,640 patient responses to structured questions. All 200 reviews from the 20 hospitals randomly selected were subjected to further quantitative and qualitative analysis. Comments about clinicians and staff were common (179 [90%]) and overwhelmingly positive, with 149 (83%) favorable to workers. In 124 (62%) of the 200 reviews, patients commented on technical aspects of hospital care, including quality of care, injuries, errors, and incorrect medical record or discharge documentation. Perceived medical errors were described in 51 (26%) hospital reviews. Comments about the hospital facility appeared in half (52%) of reviews, describing hospital cleanliness, food, parking, and amenities. Hospitals replied to 56% of the patient reviews. NHS Choices represents the first government-run initiative that enables any patient to provide narrative feedback about hospital care. Reviews appear to have similar domains to those covered in existing satisfaction surveys but also include detailed feedback that would be unlikely to be revealed by such surveys. Online narrative reviews can therefore provide useful and complementary information to consumers (patients) and hospitals, particularly when combined with systematically collected patient experience data.


Contemporary climate change and terrestrial invertebrates: evolutionary versus plastic changes.
To forecast the responses of species to future climate change, an understanding of the ability of species to adapt to long-term shifts in temperature is crucial. We present a review on evolutionary adaptation and phenotypic plasticity of temperature-related traits in terrestrial invertebrates. The evidence for adaptive evolution in melanization is good, but we caution that genetic determination needs to be tested in each individual species, and complex genetic correlations may exist. For phenological traits allochronic data sets provide powerful means to track climate-induced changes; however, rarely are responses deconstructed into evolutionary and plastic responses. Laboratory studies suggest climate change responses in these traits will be driven by both. For stress resistance, the evidence for shifts in traits is poor. Studies leaning heavily on Drosophila have demonstrated potential limits to evolutionary responses in desiccation and heat resistance. Quantifying the capacity for these species to respond plastically and extending this work to other taxa will be an important next step. We also note that, although not strictly speaking a species trait, the response of endosymbionts to heat stress requires further study. Finally, while clearly genetic, and possibly adaptive, the anonymous nature of latitudinal shifts in clines of genetic markers in Drosophila prevents further interpretation.


Pathophysiologic and therapeutic importance of tissue ACE: a consensus report.
Angiotensin-converting enzyme (ACE) activation and the de novo production of angiotensin II contribute to cardiovascular disease through direct pathological tissue effects, including vascular remodeling and inflammation, as well as indirect action on nitric oxide bioavailability and its consequences. The endothelium plays a pivotal role in both vascular function and structure; thus, the predominant localization of ACE to the endothelium has implications for the pathobiology of vascular disease, such as coronary artery disease. Numerous experimental studies and clinical trials support the emerging realization that tissue ACE is a vital therapeutic target, and that its inhibition may restore endothelial function or prevent endothelial dysfunction. These effects exceed those attributable to blood pressure reduction alone; hence, ACE inhibitors may exert an important part of their effects through direct tissue action. Pharmacologic studies show that while ACE inhibitors may differ according to their binding affinity for tissue ACE the clinical significance remains to be determined.


Investigating the multi-causal and complex nature of the accident causal influence of construction project features.
Construction project features (CPFs) are organisational, physical and operational attributes that characterise construction projects. Although previous studies have examined the accident causal influence of CPFs, the multi-causal attribute of this causal phenomenon still remain elusive and thus requires further investigation. Aiming to shed light on this facet of the accident causal phenomenon of CPFs, this study examines relevant literature and crystallises the attained insight of the multi-causal attribute by a graphical model which is subsequently operationalised by a derived mathematical risk expression that offers a systematic approach for evaluating the potential of CPFs to cause harm and consequently their health and safety (H&S) risk implications. The graphical model and the risk expression put forth by the study thus advance current understanding of the accident causal phenomenon of CPFs and they present an opportunity for project participants to manage the H&S risk associated with CPFs from the early stages of project procurement.


Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.
Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs) in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5)). To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651) were associated with increased risk for bladder cancer: odds ratio (95% confidence interval): 2.52 (1.06-5.97), 2.74 (1.26-5.98), and 3.02 (1.36-6.63), respectively; and a polymorphism in intron 2 (rs3024994) was associated with reduced risk: 0.65 (0.46-0.91). Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively). These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.


Treatment of severe inflammatory root resorption in a young permanent incisor with mineral trioxide aggregate.
Inflammatory root resorption is a pathologic condition caused by several etiologic factors including traumatic dental injury. In this case report, we describe treatment of a maxillary lateral incisor affected by severe, perforating inflammatory root resorption. An 11-year-old patient presented with a previously traumatized, root-filled maxillary lateral incisor associated with pain, mobility and a sinus tract. Radiographic examination revealed a large periradicular lesion involving pathologic resorption of the apical region of the root. After removal of the root canal filling, the tooth was treated with intracanal calcium hydroxide for 2 weeks. The calcium hydroxide dressing was then removed and the entire root canal was filled with mineral trioxide aggregate. The endodontic access cavity was restored with composite resin. After 1 year, advanced osseous healing of the periradicular region had occurred and no clinical symptoms were apparent.


Direct evidence for control of the pheromone-inducible prgQ operon of Enterococcus faecalis plasmid pCF10 by a countertranscript-driven attenuation mechanism.
The mating response of Enterococcus faecalis cells carrying the conjugative plasmid pCF10 is controlled by multiple regulatory circuits. Initiation of transcription of the prgQ conjugation operon is controlled by the peptide receptor protein PrgX; binding of the pheromone peptide cCF10 to PrgX abolishes PrgX repression, while binding of the inhibitor peptide iCF10 enhances repression. The results of molecular analysis of prgQ transcripts and genetic studies suggested that the elongation of prgQ transcripts past a putative terminator (IRS1) may be controlled by the interaction of nascent prgQ mRNAs with a small antisense RNA (Anti-Q) encoded within prgQ. Direct evidence for interaction of these RNAs, as well as the resulting effects on readthrough of prgQ transcription, has been limited. Here we report the results of experiments that (i) determine the inherent termination properties of prgQ transcripts in the absence of Anti-Q; (ii) determine the direct effects of the interaction of Anti-Q with nascent prgQ transcripts in the absence of complicating effects of the PrgX protein; and (iii) begin to dissect the structural components involved in these interactions. The results confirm the existence of alternative terminating and antiterminating forms of nascent prgQ transcripts in vivo and demonstrate that the interaction of Anti-Q with these transcripts leads to termination via inhibition of antiterminator formation. In vitro transcription assays support the major results of the in vivo studies. The data support a model for Anti-Q function suggested from recent studies of these RNAs and their interactions in vitro (S. Shokeen, C. M. Johnson, T. J. Greenfield, D. A. Manias, G. M. Dunny, and K. E. Weaver, submitted for publication).


Molecular investigation of the wettability of rough surfaces using molecular dynamics simulation.
In the present study, a computational investigation on the effect of surface roughness on the wettability behavior of water nanodroplets has been performed via molecular dynamics simulation. To fabricate the roughness, several grooves with different depths and widths were considered on the top layer(s) of graphite. Free energy analysis indicates that surface roughness reduces the solid-liquid adhesion and the work done for the removal of the nanodroplet from the solid surface. This reduction increases with an increase in both the depth and width of the grooves. Furthermore, the adhesion in Wenzel state is greater than that in the Cassie-Baxter state. Results show that increasing the depth and decreasing the width of the grooves decrease the wettability and the nanodroplet locates in the Cassie-Baxter state. In addition, both the Cassie-Baxter and Wenzel models effectively predict the nanodroplet contact angle on the rough surfaces. Furthermore, the probability of successful interactions decreases in the solid-liquid interfaces due to the heterogeneity of the surface. Therefore, the density, the residence time and the hydrogen bond lifetime of the water molecules in the layer in the vicinity of the substrate decrease. In addition, surface roughness affects the orientation of the water molecules at the interface, the diffusion of water molecules as well as the movement of the water nanodroplet.


[Temperament as a prerequisite of creative capabilities].
Temperamental and creative characteristics were compared in three groups of subjects who manifested a bent for creative activity. The groups differed in their age: 14-year-old schoolchildren of architectural class (n = 20), 18 to 20-year-old students of architectural institute (n = 94), and 25 to 45-year-old professional architects (n = 25). The temperamental properties were measured using the STQ method. The creative characteristics were evaluated by E. P. Torrance's non-verbal tests of creative thinking. In the structure of creative abilities, only two creative characteristics, i.e., fluency and flexibility, correlated at the statistically significant level with temperamental properties in all the age-specific groups under study. The closest correlations were found with plasticity and emotionality of temperament both in object-related and subject-related spheres.


Childhood correlates of adult positive mental well-being in three British longitudinal studies.
Previous evidence has shown how experiences within childhood, such as parenting and socioeconomic conditions, are associated later on in life with adult mental well-being. However, these studies tend to focus on childhood experiences in isolation, and fewer studies have investigated how multiple aspects of the childhood environment, including both socioeconomic and psychosocial aspects, are associated with adult positive mental well-being. Using data from three British birth cohort studies, we investigated how prospective measures of the childhood environment up to the age of 16 years were associated with midlife adult mental well-being and whether similar associations were replicated across different generations. Childhood environment comprised socioeconomic circumstances, psychosocial factors (child-rearing and parenting, family instability) and parental health. The Warwick-Edinburgh Mental Wellbeing Scale, a validated instrument measuring both hedonic and eudaemonic aspects of well-being, was administered in mid-life. We modelled associations between childhood environment domains and well-being. Despite changes in social context in all three studies, poorer quality parent-child relationships and poor parental mental health were strongly and independently associated with poorer adult mental well-being. Socioeconomic circumstances were also associated with adult mental well-being, but the association was weaker than for the measures of parenting or parental mental health. These findings confirm that parenting and parental mental health, as well as socioeconomic circumstances, are important for adult mental well-being. Interventions in early childhood aimed at reducing socioeconomic adversity and offering support to parents might be warranted, to enhance adult mental well-being later on in the life course.


Characterisation of different morphological features of black tiger shrimp (Penaeus monodon) haemocytes using monoclonal antibodies.
Monoclonal antibodies (mabs) specific for Penaeus monodon haemocytes were produced by immunising mice with membrane lysates of shrimp haemocytes. Four mabs (WSH 6, WSH 7, WSH 8 and WSH 16) were characterised using flow cytometry, light microscopy, laser scanning microscopy, electron microscopy and immunoprecipitation. WSH 6 recognised a carbohydrate determinant on an 85 kDa molecule. WSH 7, WSH 8 and WSH 16 recognised 50, 35 and 115 kDa molecules, respectively. For all mabs, differences in amount and intensity of the labelling were found when haemocytes were fixed immediately in 2% formaldehyde in Alsever's Solution (AS), compared with non-fixed haemocytes that were kept in AS (which reduced activation of the haemocytes) or in L15 cell culture medium. WSH 6 reacted with the cell membranes of all fixed haemocytes, while WSH 7 and WSH 16 reacted with the cell membranes of >80% of fixed haemocytes. The membrane labelling appeared to decrease when cells were kept in L15 medium. WSH 8 did not react with the haemocyte membranes. All mabs reacted with some granules, mainly present in the hyaline cells, when the haemocytes were immediately fixed. When non-fixed cells were kept in AS and in L15 medium, positive granules were also observed in semigranular and granular haemocytes as well as in the largest granules of a fourth cell type, that contains many granules of different size and electron density. Immunoreactive extracellular thread-like material could be observed in cells in L15 medium. The change in staining pattern was extreme for WSH 8, somewhat less for WSH 6 and WSH 7 and the lowest for WSH 16. Double labelling revealed that all mabs showed a different staining pattern on membranes as well as on granules. WSH 16 also showed labelling in cytoplasmic vesicles, as well as in haemolymph plasma on histological sections. The hypothesis is put forward that immunoreactive molecules recognised by these mabs, are related to haemocyte activation factors.


Leprosy in Sydney: a brief account.
Individuals with leprosy and those incubating the disease continue to enter New South Wales from endemic areas. With early diagnosis and treatment, the prognosis is good. The diagnosis should be considered in any patient who has lived or worked in a leprosy endemic country and who presents with an unusual or persistent skin erpution (especially if there is associated hypoaesthesia) and/or mononeuritis or mononeuritis multiplex. Occasionally the disease presents inother guises; biopsy of the appropriate tissue and staining for acid-fact bacilli, as well as haematoxylin and eosin, will usually indicate the correct diagnosis.


Current-generating 'double layer shoe' with a porous sole.
We present a principle and a simple theory of a novel reverse electroactuator, in which the electrical current is generated by pumping an electrolytic liquid into nonwetting pores of a polarized electrode. The theory establishes the relationship between the variation of external pressure and the electrical current. The effective current density is amplified by the high porosity of the electrode. The suggested principle can be implemented into the design of a shoe which will generate an AC current simply by walking. Estimates of typical parameters and operation regimes of such a device suggest that one can easily generate a peak current density of ~17 mA cm(-2). This would produce some 1.7 A from each shoe at 0.65 W average power density, without hampering walking.


Experimental annotation of the human genome using microarray technology.
The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.


Towards a population-based threshold of protection for COVID-19 vaccines.
Correlates of protection for COVID-19 vaccines are urgently needed to license additional vaccines. We measured immune responses to four COVID-19 vaccines of proven efficacy using a single serological platform. IgG anti-Spike antibodies were highly correlated with ID50 neutralization in a validated pseudoviral assay and correlated significantly with efficacies for protection against infection with wild-type, alpha and delta variant SARS-CoV-2 virus. The protective threshold for each vaccine was calculated for IgG anti-Spike antibody. The mean protective threshold for all vaccine studies for WT virus was 154 BAU/ml (95 %CI 42-559), and for studies with antibody distributions that enabled precise estimation of thresholds (i.e. leaving out 2-dose mRNA regimens) was 60 BAU/ml (95 %CI 35-102). We propose that the proportion of individuals with responses above the appropriate protective threshold together with the geometric mean concentration can be used in comparative non-inferiority studies with licensed vaccines to ensure that new vaccines will be efficacious.


Evaluation of Pseudosel agar as an aid in the identification of Pseudomonas aeruginosa.
Growth of Pseudomonas aeruginosa and thirty-five other species of gramnegative bacilli was observed on 0.03% cetrimide in heart infusion agar medium and Pseudosel agar (BBL). The 0.03% cetrimide agar was more selective for growth of P. aeruginosa than was Pseudosel agar; however, certain bacteria other than P. aeruginosa also grew on the former medium. Although Pseudosel agar was not a highly selective medium for P. aeruginosa, it was preferable to technicolor agar for detection of the pyocyanin and pyorubin pigments produced by P. aeruginosa.


Experiences of daily life and oral rehabilitation in oligodontia - a qualitative study.
Quantitative research indicate increased anxiety and poorer mental health related quality of life (QoL) in individuals with oligodontia (congenital absence of six or more teeth). The aim of this qualitative study was to complement and explore the individuals' experiences of life and oral rehabilitation, hopefully improving the care for these patients. Twelve participants (6 females, 6 males, aged 21-48) with oligodontia and experiences of comprehensive dental treatments, consented to participate in a semi-structured interview. The questions in the interview guide were based on previous research and clinical experience and included both open (i.e. how is your life?) and specific questions (i.e. do health care personnel know enough about your condition?). The interview transcripts were coded and analysed using a phenomenological method of analysis. The Regional Ethics Committee approved the study. The following themes grew out of the data; 'feeling of being different', 'the burden of treatment', 'shared decision-making', 'treatment increases self-esteem' and 'use of coping strategies'. Psychological distress and reduced QoL seemed to be related to negative aspects of the themes, which covered unacceptable aesthetics, reduced orofacial function, the long-term process of oral rehabilitation, and negative experiences with healthcare services. The informants used problem focused and emotionally focused strategies to meet these challenges. Finalizing oral rehabilitation and shared decision making were positive aspects of the themes. All themes expressed by the participants were of importance for experienced QoL and psychological distress, and should be acknowledged by health care personnel when planning and performing treatment.


Baseline visual field findings in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).
To characterize visual field (VF) loss at the baseline visit and to evaluate VF quality control (QC) procedures in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). The Visual Field Reading Center (VFRC) evaluated 660 baseline VFs (1320 hemifields) from 165 enrolled patients. Three readers independently classified each superior and inferior hemifield and identified any abnormalities. A subset (20%) of the hemifields was reread to evaluate within- and between-reader agreements. The QC system addressed test parameters, patient data, and shipment errors. The majority (60%) of the baseline hemifields consisted of localized nerve fiber bundle-type VF loss. Approximately one-third (31.5%) of all the classifications consisted of partial arcuate defects combined with an enlarged blind spot, making this the most common type of hemifield classification. Inferior hemifield loss was greater than superior loss for both study and nonstudy eyes. Reader agreements were >90% for both inferior and superior hemifields for two out of three readers. Test-retest reliability agreement for individual readers was 95% for both hemifields. There were few QC errors with only 5.48 error points per 100-point VF. The most common type of IIHTT baseline hemifield abnormality was a localized nerve fiber bundle-like defect. Localized inferior hemifield loss was more common than superior hemifield loss. Quality control and within- and between-reader agreement were excellent for the IIHTT (ClinicalTrials.gov number, NCT01003639).


Coronal CT scan abnormalities in children with chronic sinusitis.
Coronal computed tomography (CT) scans are currently the optimal study to display the normal and abnormal anatomy in children with chronic and recurrent acute sinusitis after failure of medical therapy. To assess the extent and distribution of disease as well as associated anatomic abnormalities in this pediatric population, 74 coronal CT scans of children with continued symptoms of sinusitis after failure of extensive medical therapy were reviewed retrospectively. Twelve children with cystic fibrosis showed the characteristic features of medial displacement of the lateral nasal wall in the middle meatus and uncinate process demineralization, creating the appearance of a maxillary sinus mucocele. Nine of these 12 children had increased attenuation in the maxillary sinus on soft-tissue windows. In the remaining 62 children, a significantly greater frequency of disease, when compared with that reported for adults, was seen in the maxillary, anterior ethmoid, posterior ethmoid, and frontal sinuses. Children with asthma (n = 33) had more extensive disease. Bony anatomic abnormalities were similar to those reported for adults, except for a lower incidence of septal deformity.


Evidence for Immune Response, Axonal Dysfunction and Reduced Endocytosis in the Substantia Nigra in Early Stage Parkinson's Disease.
Subjects with incidental Lewy body disease (iLBD) may represent the premotor stage of Parkinson's disease (PD). To elucidate molecular mechanisms underlying neuronal dysfunction and alpha-synuclein pathology in the premotor phase of PD, we investigated the transcriptome of the substantia nigra (SN) of well-characterized iLBD, PD donors and age-matched controls with Braak alpha-synuclein stage ranging from 0-6. In Braak alpha-synuclein stages 1 and 2, we observed deregulation of pathways linked to axonal degeneration, immune response and endocytosis, including axonal guidance signaling, mTOR signaling, EIF2 signaling and clathrin-mediated endocytosis in the SN. In Braak stages 3 and 4, we observed deregulation of pathways involved in protein translation and cell survival, including mTOR and EIF2 signaling. In Braak stages 5 and 6, we observed deregulation of dopaminergic signaling, axonal guidance signaling and thrombin signaling. Throughout the progression of PD pathology, we observed a deregulation of mTOR, EIF2 and regulation of eIF4 and p70S6K signaling in the SN. Our results indicate that molecular mechanisms related to axonal dysfunction, endocytosis and immune response are an early event in PD pathology, whereas mTOR and EIF2 signaling are impaired throughout disease progression. These pathways may hold the key to altering the disease progression in PD.


[Concentration dependence of luminescence under different excitation wavelength in Y2O2S:Sm3+ phosphor].
The concentration dependence of luminescence under different excitations in Y2O2S:Sm3+ phosphor has been studied. The optimum activator concentration was found to be a function of the number of excited activator ions as well as the excitation wavelength. The concentration dependence curve of Y2O2S:Sm3+ phosphor under 413 nm excitation was different from the curve obtained with 263 nm excitation. For excitation radiation having longer wavelength (413 nm), the concentration quenching of Y2O2S:Sm3+ phosphor occurred at about 2%, which is ten times the result with shorter wavelength (263 nm) excitation (-0.2%). Fitting the concentration dependence curve and the result shows that the cross-relaxation caused by the dipole-quadrupole interaction of neighboring Sm3+ ions results in the concentration quenching.


Effect of ginsenoside Rg1 on proliferation and neural phenotype differentiation of human adipose-derived stem cells in vitro.
To investigate whether ginsenoside Rg1 can promote neural phenotype differentiation of human adipose-derived stem cells (hASCs) in vitro. hASCs were isolated from lipo-aspirates, and characterized by specific cell markers and multilineage differentiation capacity after culturing to the 3rd passage. Cultured hASCs were treated with neural inductive media alone (group A, control) or inductive media plus 10, 50, or 100 μg/mL ginsenoside Rg1 (groups B, C, and D, respectively). Cell proliferation was assessed by CCK-8 assay. Neuron specific enolase (NSE) and microtubule-associated protein-2 (MAP-2) levels were measured by Western blot. mRNA levels of growth associated protein-43 (GAP-43), neural cell adhesion molecule (NCAM), and synapsin-1 (SYN-1) were determined by real-time PCR. Ginsenoside Rg1 promoted the proliferation of hASCs (groups B, C, and D) and resulted in higher expression of NSE and MAP-2 compared with the control group. Gene expression levels of GAP-43, NCAM, and SYN-1 in the test groups were higher than that in thw control. The results displayed a dose-dependent effect of ginsenoside Rg1 on cell proliferation and neural phenotype differentiation. This study indicated that ginsenoside Rg1 promotes cell proliferation and neural phenotype differentiation of hASCs in vitro, suggesting a potential use for hASCs in neural regeneration medicine.


A counterexample to a diameter algorithm for convex polygons.
Recently, Snyder and Tang [1] proposed an algorithm for finding the diameter of a convex polygon. In this note a family of convex polygons is described for which their algorithm fails. It is also pointed out that the diameter of an arbitrary simple n-vertex polygon can be computed in O(n) time.


Antigen-induced stimulation of glucosamine incorporation by guinea pig peritoneal macrophages in delayed hypersensitivity.
The interaction between sensitized lymphocytes and specific antigen occurring in delayed hypersensitivity causes bystander macrophages to undergo a variety of light-microscopic, ultrastructural, and biochemical changes, which are reflected in alterations in cell movement and intercellular contacts. Since such alterations involve functions of the cell periphery, we postulated that metabolic changes in this polysaccharide-rich zone would accompany the expression of delayed hypersensitivity. We here demonstrate that the incorporation of radioactive glucosamine by peritoneal macrophages into TCA-precipitable, membrane-associated material is regularly enhanced when these are cultured in the presence of specific antigen and nonadherent cells (lymphocytes) primed for delayed hypersensitivity. Lymphocytes from unsensitized animals, or from animals immunized so as to form antibody but not delayed hypersensitivity, do not stimulate such incorporation. Antigen-induced glucosamine incorporation is maximal at 2 or 3 days of culture and is not observed earlier; it may be elicited with as little as 0.1 microg/ml PPD, and affords an exceedingly reproducible and sensitive index of delayed hypersensitivity. Radioautographic studies indicate that nearly all plastic adherent cells (90% macrophages) incorporate glucosamine and that grains are concentrated in the regions of the perinuclear zone and cell membrane. Subcellular fractionation indicates that nearly 30% of counts and the highest specific activity are associated with the membrane-rich microsomal fraction; the microsomal distribution of counts increases in both absolute and relative terms when macrophages are cultured in the presence of specific antigen and sensitized lymphocytes. Taken together, these data indicate that a sizable fraction of incorporated glucosamine is localized to the vicinity of the cell periphery but lack sufficient resolution to determine whether this material is associated with the cell membrane itself or with the extramembranous cell coat. This last possibility is of particular interest since we have previously shown that macrophage cell coat material is lost or altered as a consequence of an interaction between sensitized lymphocytes and specific antigen.


Validation of a yeast functional assay for p53 mutations using clonal sequencing.
We have previously tested biopsies from 1469 breast tumours with a p53 functional assay in the context of a prospective clinical trial (EORTC 10994/BIG 1-00). The goal of the trial was to determine whether p53 status could be used to select patients who would benefit from inclusion of taxanes in anthracycline-based chemotherapy. The results of the trial were negative. To test whether this was because the functional assay misclassified the tumours, we have reanalysed two groups of biopsies by Sanger sequencing and Roche 454 next generation sequencing (NGS). Comparison of yeast data with pooled cDNA sequencing data in an initial cohort of 69 biopsies showed that conventional sequencing is insensitive when the mutant p53 content is low. A second cohort of 48 biopsies was used to compare directly the yeast assay with Sanger and NGS technology. The mutant sequence was difficult to detect in sequence chromatograms of pooled cDNA, whereas NGS unequivocally identified mutations in every case classified as mutant by the functional assay. The NGS data showed that small deletions, probably caused by PCR splicing, account for most of the unexplained background in the yeast assay. We conclude that mutation detection techniques that test multiple clones, such as the p53 functional assay and NGS, are more reliable than Sanger sequencing of pooled DNA; that the high p53 mutation rate (44%) seen with the yeast assay in the EORTC 10994/BIG 1-00 trial reflects this high sensitivity; and that NGS with Roche 454 technology could be used to identify the p53 mutations in the remaining tumours previously tested in yeast in the EORTC10994/BIG 1-00 trial.


Identification of a Nine-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Cancer.
Background: Pancreatic cancer is highly lethal and aggressive with increasing trend of mortality in both genders. An effective prediction model is needed to assess prognosis of patients for optimization of treatment. Materials and Methods: Seven datasets of mRNA expression and clinical data were obtained from gene expression omnibus (GEO) database. Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas pancreatic ductal adenocarcinoma (TCGA-PAAD) dataset. Differentially expressed genes (DEGs) between pancreatic tumor and normal tissue were identified by integrated analysis of multiple GEO datasets. Univariate and Lasso Cox regression analyses were applied to identify overall survival-related DEGs and establish a prognostic gene signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell's concordance index (C-index) and calibration curve. GSE62452 and GSE57495 were used for external validation. Gene set enrichment analysis (GSEA) and tumor immunity analysis were applied to elucidate the molecular mechanisms and immune relevance. Multivariate Cox regression analysis was used to identify independent prognostic factors in pancreatic cancer. Finally, a prognostic nomogram was established based on the TCGA PAAD dataset. Results: A nine-gene signature comprising MET, KLK10, COL17A1, CEP55, ANKRD22, ITGB6, ARNTL2, MCOLN3, and SLC25A45 was established to predict overall survival of pancreatic cancer. The ROC curve and C-index indicated good performance of the nine-gene signature at predicting overall survival in the TCGA dataset and external validation datasets relative to classic AJCC staging. The nine-gene signature could classify patients into high- and low-risk groups with distinct overall survival and differentiate tumor from normal tissue. Univariate Cox regression revealed that the nine-gene signature was an independent prognostic factor in pancreatic cancer. The nomogram incorporating the gene signature and clinical prognostic factors was superior to AJCC staging in predicting overall survival. The high-risk group was enriched with multiple oncological signatures and aggressiveness-related pathways and associated with significantly lower levels of CD4+ T cell infiltration. Conclusion: Our study identified a nine-gene signature and established a prognostic nomogram that reliably predict overall survival in pancreatic cancer. The findings may be beneficial to therapeutic customization and medical decision-making.


Functional independency between catalytic activity and subcellular targeting of polo-like kinase-1: phenotypes of ectopic overexpression of various mutants.
The mammalian polo-like kinase-1 (Plk1) plays key role in the progression of the M-phase. As cells enter the M-phase, Plk1 is phosphorylated by an upstream kinase on Thr-210 in N-terminal region, which is essential for Plk1 activation. In addition to catalytic activation, the subcellular localization is also an important task for Plk1, and the C-terminal polo-boxes are responsible for Plk1 targeting. Although both catalytic activation and targeting might be essential and work concurrently, it is still unclear which process precedes the other in mitotic progression, and which is more essential for the function of Plk1 through the M-phase. In order to investigate this mechanism, this study introduced several point mutations in the catalytic and polo-box domains, and overexpressed these constructs in HeLa cells. Although the cellular effects by ectopic expression were different in the cells containing various Plk1 constructs, phosphorylation itself, not the catalytic activity, was found to be important for the progression of the M-phase. Plk1 phosphorylation was also responsible for targeting by polo-box, and compensated for the polo-box mutation. These results suggested that Plk1 is phosphorylated in the starting M-phase, and this phosphorylation induces polo-box targeting through a possible conformational change. In this situation, catalytic activation does not appear to be a critical factor for the function of Plk1.


Cellular and Molecular Biomarkers Indicate Premature Aging in Pseudoxanthoma Elasticum Patients.
The molecular processes of aging are very heterogenic and not fully understood. Studies on rare progeria syndromes, which display an accelerated progression of physiological aging, can help to get a better understanding. Pseudoxanthoma elasticum (PXE) caused by mutations in the ATP-binding cassette sub-family C member 6 (ABCC6) gene shares some molecular characteristics with such premature aging diseases. Thus, this is the first study trying to broaden the knowledge of aging processes in PXE patients. In this study, we investigated aging associated biomarkers in primary human dermal fibroblasts and sera from PXE patients compared to healthy controls. Determination of serum concentrations of the aging biomarkers eotaxin-1 (CCL11), growth differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF1) showed no significant differences between PXE patients and healthy controls. Insulin-like growth factor binding protein 3 (IGFBP3) showed a significant increase in serum concentrations of PXE patients older than 45 years compared to the appropriate control group. Tissue specific gene expression of GDF11 and IGFBP3 were significantly decreased in fibroblasts from PXE patients compared to normal human dermal fibroblasts (NHDF). IGFBP3 protein concentration in supernatants of fibroblasts from PXE patients were decreased compared to NHDF but did not reach statistical significance due to potential gender specific variations. The minor changes in concentration of circulating aging biomarkers in sera of PXE patients and the significant aberrant tissue specific expression seen for selected factors in PXE fibroblasts, suggests a link between ABCC6 deficiency and accelerated aging processes in affected peripheral tissues of PXE patients.


Nucleosome Positioning around Transcription Start Site Correlates with Gene Expression Only for Active Chromatin State in Drosophila Interphase Chromosomes.
We analyzed the whole-genome experimental maps of nucleosomes in Drosophila melanogaster and classified genes by the expression level in S2 cells (RPKM value, reads per kilobase million) as well as the number of tissues in which a gene was expressed (breadth of expression, BoE). Chromatin in 5'-regions of genes we classified on four states according to the hidden Markov model (4HMM). Only the Aquamarine chromatin state we considered as Active, while the rest three states we defined as Non-Active. Surprisingly, about 20/40% of genes with 5'-regions mapped to Active/Non-Active chromatin possessed the minimal/at least modest RPKM and BoE. We found that regardless of RPKM/BoE the genes of Active chromatin possessed the regular nucleosome arrangement in 5'-regions, while genes of Non-Active chromatin did not show respective specificity. Only for genes of Active chromatin the RPKM/BoE positively correlates with the number of nucleosome sites upstream/around TSS and negatively with that downstream TSS. We propose that for genes of Active chromatin, regardless of RPKM value and BoE the nucleosome arrangement in 5'-regions potentiates transcription, while for genes of Non-Active chromatin, the transcription machinery does not require the substantial support from nucleosome arrangement to influence gene expression.


Chronic Cranial Windows for Long Term Multimodal Neurovascular Imaging in Mice.
Chronic cranial windows allow for longitudinal brain imaging experiments in awake, behaving mice. Different imaging technologies have their unique advantages and combining multiple imaging modalities offers measurements of a wide spectrum of neuronal, glial, vascular, and metabolic parameters needed for comprehensive investigation of physiological and pathophysiological mechanisms. Here, we detail a suite of surgical techniques for installation of different cranial windows targeted for specific imaging technologies and their combination. Following these techniques and practices will yield higher experimental success and reproducibility of results.


The elasticity of cervical-vaginal secretions is abnormal in polycystic ovary syndrome: Case report of five PCOS women.
Polycystic Ovary Syndrome (PCOS) is a leading cause of infertility. We studied the rheological properties of cervical-vaginal secretions in five PCOS patients during variable treatment intervals with metformin. Five ovulatory normal women for a total of thirteen cycles served as control patients. All subjects collected daily cervical-vaginal fluid(CVF) samples with an aspirator, and CVF samples were characterized by a flow metric, die swell ratio (B), which measured CVF elasticity. Ovulatory cycles were indexed to the day of positive urine or serum LH (luteinizing hormone). CVF B levels from ovulatory normal women had a characteristic concave parabolic pattern of a minimum near the day of ovulation with higher values outside the periovulatory phase. In contrast, the five PCOS patients with or without metformin treatment had no periodicity of CVF B, and their CVF B levels were typically less compared to those in the early preovulatory and luteal phases of normal patients.


Non-invasive assessment of cardiac function in meningitis.
Non-invasive registration of systolic time intervals (STI) and ECG were used in evaluating cardiac function in 12 patients with bacterial and 16 with viral meningitis. On admission, 14 (50%) of the patients had abnormal STI. The preejection period (PEP) was prolonged in 11 patients, while left ventricular ejection time (LVET) was prolonged in two and shortened in four. The PEP/LVET index was increased in eight patients. At discharge PEP was still prolonged in eight patients; seven of these were from the viral meningitis group. LVET increased significantly (p less than 0.02) from the first to the last registration. In the patients with abnormal PEP and PEP/LVET on admission, there was a significant fall (p less than 0.05 and p = 0.02, respectively) to discharge. There was no difference in STI between the patients with viral or bacterial meningitis. Eighteen (64%) of the patients had abnormal STI on one or more registration. ST-T changes in ECG and prolongation of the Q-T interval were found in three patients. Cardiac affection in meningitis seems to occur more often than can be shown by ECG.


Development of real-time PCR assays for detection of the Streptococcus milleri group from cystic fibrosis clinical specimens by targeting the cpn60 and 16S rRNA genes.
Cystic fibrosis (CF) is a multiorgan disease, with the majority of mortalities resulting from pulmonary failure due to repeated pulmonary exacerbations. Recently, members of the Streptococcus anginosus group (S. anginosus, S. constellatus, and S. intermedius), herein referred to as the "Streptococcus milleri group" (SMG) have been implicated as important etiological pathogens contributing to pulmonary exacerbations in CF patients. This is partly due to better microbiological detection of the SMG species through the development of a novel specific medium termed "McKay agar." McKay agar demonstrated that SMG has been an underreported respiratory pathogen contributing to lung exacerbations. Our aim was to develop a real-time PCR assay to expedite the detection of SMG within diagnostic samples. The cpn60 gene was chosen as a target, with all three members amplified using a single hybridization probe set. SMG strain analysis showed that speciation based on melting curve analysis allowed for the majority of the S. constellatus (96%), S. intermedius (94%), and S. anginosus (60%) strains to be correctly identified. To increase specificity for S. anginosus, two 16S rRNA real-time PCR assays were developed targeting the 16S rRNA gene. The 16s_SA assay is specific for S. anginosus (100%), while the 16s_SCI assay is specific for S. constellatus and S. intermedius (100%). These assays can detect <10 genome equivalents in pure culture and >10(4) genome equivalents in sputum samples, making this a great tool for assessment of the presence of SMG in complex polymicrobial samples. Novel molecular methods were developed providing detection ability for SMG, an emerging opportunistic pathogen.


Follicle-stimulating hormone and estradiol interact to stimulate glutathione synthesis in rat ovarian follicles and granulosa cells.
Glutathione (GSH), the most abundant intracellular nonprotein thiol, is critical for many cellular functions. The rate-limiting step in GSH synthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimer composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The tissue-specific regulation of GSH synthesis is poorly understood. We showed previously that gonadotropin hormones regulate ovarian GSH synthesis. In the present study, we sought to clarify the ovarian cell type-specific effects of follicle-stimulating hormone (FSH) and estradiol on GSH synthesis. Immature female rats were treated with estradiol to stimulate development of small antral follicles. Granulosa cells (GCs) from these follicles or whole follicles were cultured in serum-free media, with or without FSH and 17beta-estradiol. The GSH and GCLC protein and mRNA levels increased in GCs treated with FSH alone. The effects of FSH on GCLC and GCLM protein and mRNA levels, GCL enzymatic activity, and GSH concentrations in GCs were significantly enhanced by the addition of estradiol. Estradiol alone had no effects on GSH. Dibromo-cAMP mimicked and protein kinase A (PKA) inhibitors prevented FSH stimulation of GCL subunit protein levels. In cultured small antral follicles, FSH stimulated estradiol synthesis and robustly increased GCL subunit mRNA and protein levels and GSH concentrations. The GCL subunit mRNA expression increased in both the granulosa cells and theca cells of follicles with FSH stimulation. These data demonstrate that maximal stimulation of GSH synthesis by FSH in granulosa cells and follicles requires estradiol. Without estradiol, FSH causes lesser increases in GCL subunit expression via a PKA-dependent pathway.


Sensitive and selective liquid chromatography/tandem mass spectrometry methods for quantitative analysis of 1-methyl-4-phenyl pyridinium (MPP+) in mouse striatal tissue.
The systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice produces a reliable and selective degeneration of the nigrostriatal pathway, a hallmark feature of Parkinson's disease (PD). Determining the brain concentrations of 1-methyl-4-phenyl pyridium (MPP+), the neurotoxic metabolite of MPTP, is critical for evaluating drugs designed to potentially treat PD. We have developed sensitive and specific quantitative methods for the determination of MPP+ in mouse striatal tissue by liquid chromatography/tandem mass spectrometry. The separations were carried out based on reversed phase chromatography or cation exchange chromatography with volatile elution buffer. Neutralizing the brain sample with 0.2M phosphate buffer successfully solved a high-performance liquid chromatography (HPLC) peak tailing of MPP+ in brain extracts with 0.4M perchloric acid (HClO4) under the reversed phase HPLC conditions, which significantly improved the sensitivity of the method. The HPLC peak shape of MPP+ using cation exchange chromatography was not affected by the pH of the samples. Optimization of electrospray ionization (ESI) conditions for the quaternary ammonium compound MPP+ established the limits of detection (LOD) (S/N=3) at 0.34pg/mg tissue and 0.007pg/mg tissue (5microl of injection) using the reversed phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) and the cation exchange LC/MS/MS, respectively. Both methods were selective, precise (%R.S.D.<6%), and sensitive over a range of 0.001-1ng/mg tissue. The cation exchange method showed greater sensitivity and tolerance to low pH samples than the reversed phase method. The developed methods were applied to monitoring changes in MPP+ concentrations in vivo. Two reference agents, R-(-) Deprenyl and MK-801, known to alter the concentration of MPP+ in MPTP treated mice were evaluated.


Self-reported injection practices among people who use drugs in French prisons: Public health implications (ANRS-Coquelicot survey 2011-2013).
The aims of this study were to describe the prevalences of injection practices and needle/syringe sharing in people who use drugs in French prisons, and to investigate associated factors. Using the ANRS-Coquelicot survey (2011-2013), a random sample of 1718 people who used drugs in free society was included. Information regarding a history of incarceration, drug-injection practices inside prison and needle/syringe sharing was collected during interviews. In our sample, 65.5% reported a history of injection and 57.4% had been incarcerated at least once. Among those who reported both of these conditions, 14% reported injection practices inside prison, 40.5% of whom had shared needles/syringes. In the multivariable model, the following variables were associated with injection practices inside prison: being a Russian-speaking detainee, having spent more time in prison, and having started to inject before 1996 and especially before 1987. Being Russian speaking was also associated with needle/syringe sharing in prison. The prevalences of injection practices and needle/syringe sharing in prisons are alarmingly high. Effective interventions to prevent the transmission of infectious diseases among people who use drugs in the prison setting are essential. The implementation of international recommendations on the principle of equivalence between prisons and the community is still very limited in most countries, and should be complemented with tailored interventions for the most vulnerable prison populations, especially Russian-speaking detainees.


Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility.
Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells. To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays. Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p<0.001) and cytoplasmic (p<0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p<0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility. Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.


Osteoporosis and polypharmacy.
Osteoporosis is very common in elderly patients. Despite the severe health-related consequences for individual patients and the socioeconomic costs caused by osteoporotic fractures, treatment rates are still low. Due to drug interactions and patient compliance, polypharmacy is often mentioned as a reason for undertreatment. Several drugs have a direct or indirect effect on bone metabolism. The present paper discusses the risk of interactions of anti-osteoporotic drugs (oral and parenteral bisphosphonates, raloxifene, strontium ranelate, teriparatide, and denosumab) with other common medications in elderly patients and their impact on bone metabolism and fracture risk. In summary, the number and risk of drug interactions of all common anti-osteoporotic drugs are small and clinically rather irrelevant. However, patients with a polypharmacy are at a higher risk of fractures and should receive osteoporosis treatment, if indicated.


Non-intubated general anesthesia in prone position for advanced biliopancreatic therapeutic endoscopy: A single tertiary referral center experience.
Advance biliopancreatic endoscopies are nowadays performed in non-operating room anesthesia (NORA) under general anesthesia (GA). We evaluate the outcomes of non-intubated patients in prone position who received GA for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) in a tertiary referral center for digestive endoscopy. Anesthesiological records, anamnestic, and intraoperative data of patients who underwent advanced therapeutic biliopancreatic endoscopies at our tertiary referral center from January 2019 until January 2020 were collected in the present observational study. One hundred fifty-three patients (93 M; median age: 68-year-old; mean ASA status: 2) were considered eligible for a procedure in the prone position with GA in spontaneous breathing. Prone position was always the initial setting. Propofol administration through a target-controlled infusion (TCI) pump was the choice to achieve GA. In our experience, desaturation appears to be the most frequent adverse event, accounting for 35% of cases (55/153). Treatment foresaw additional oxygen through a nasopharyngeal catheter, which proved to be a sufficient measure in almost all patients (52/55). Other adverse events (i.e., inadequate sedative plan, pain, and bradycardia) accounted for 2.6% of cases (4/153). Non-intubated GA in the prone position may be regarded as a safe procedure, as long as the anesthesiological criteria of exclusion are respected and the anesthesiological team has become acquainted with the peculiar NORA setting and familiar with the management of possible adverse events.


Cilia in the nervous system: linking cilia function and neurodevelopmental disorders.
Ciliopathies are genetic disorders caused by defects of primary ciliary structure and/or function and are characterized by pleiotropic clinical features. The ciliopathies include several partially overlapping syndromes such as Joubert syndrome, Bardet-Biedl syndrome and Meckel-Gruber syndrome, all of which have pronounced neurodevelopmental features. Here we focus on potential roles of cilia in central nervous system function, to explore how impairments may cause brain malformation and neurodevelopmental disease. Cilia have long been considered as 'sensory cellular antennae', responding as chemo-sensors, mechano-sensors and thermo-sensors, although their roles in development were not well understood until recently. The surprising finding that disparate syndromes are all due to defects of the primary cilia, along with the recent advances in genetics, has helped elucidate further roles of primary cilia beyond sensory functions. Several molecules that are associated with key signaling pathways have been discovered in primary cilia. These include sonic hedgehog, wingless, planar cell polarity and fibroblast growth factor, which are essential for many cellular processes. Additionally, mutations in 'ciliome' genes have largely shown developmental defects such as abnormal body axis and brain malformation, implying disrupted cilia-related signaling pathways. Accordingly, the emerging theme is that primary cilia may play roles as modulators of signal transduction to help shape cellular responses within the environmental context during both development and homeostasis. The link between cilia and signal pathways has become a framework for understanding the pathogenesis of ciliopathies. Despite recent progress in ciliary biology, fundamental questions remain about how cilia regulate neuronal function in the central nervous system. Therefore, investigation of ciliary function in the nervous system may reveal cilia-modulating mechanisms in neurodevelopmental processes, as well as suggest new treatments for disease.


Carbon coated polyethylene: effect of surface energetics and topography on human platelet adhesion.
The influence of surface energy and structural properties of carbon coated polyethylene (PE) on the human platelet adhesion was studied. Three types of amorphous carbon coating were obtained by plasma pulse discharge, with the number of pulses grading as 10, 50, 100. Human serum albumin adsorption experiments have been carried out with all samples in vitro. Platelet adhesion analysis by SEM included determination of total quantity of adherent platelets, and respective quantities of platelets at different stages of activation (single, spread, aggregates). Surface topographies ranged from bare PE and such (10 pulses), to globular 0.5 microm in size (50 pulses), and complex fibrillar 3-4 microm structures (100 pulses). Surface free energy varies from 31.7 +/- 0.6 to 40.4 +/- 0.6 mN/m for uncoated PE and 10 pulse coatings, respectively, as determined by contact angle techniques. All studied coatings demonstrate weaker platelet activation properties in comparison with untreated PE. Among all studied coatings, the 50 pulse coated surface seems to be the least suitable for contact with platelets, mainly due to its structural rather than to its energy properties. These data are related to a sharp decrease in the adsorbed protein level for the samples with 50 pulse coatings. The applied analysis of platelet activation enables more accurate characterization of platelet-biomaterial interaction.


Clinical decision making based on radionuclide determined ejection fraction in oncology patients.
Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy. A resting LVEF of 50% is usually used as the lower limit of normal values. The decision to change chemotherapy, however, is complex and is affected by many factors, including ejection fraction. To determine how LVEF data were used by clinical oncologists in clinical decision making, we performed a retrospective analysis of patients referred for ejection fraction measurements from the hematology/oncology divisionS of Stanford University from March 1992 through March 1995. The records of 565 patients treated with potentially cardiotoxic chemotherapy were evaluated. LVEFs < 50% were found in 153 patients. The charts of patients with reduced ejection fractions were reviewed to determine if the radionuclide measurement resulted in either discontinuation of the cardiotoxic agent or substitution of a less cardiotoxic drug or mode of administration. These specific changes in therapy occurred in only 43 of the 153 (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection fractions < or = 40%. Patients with lower ejection fraction values were more likely to have their therapy changed than those with LVEFs close to normal. Patients with ejection fractions < or = 30 generally had cardiotoxic agents discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not changed, 81% had a normal increase in LVEF with exercise. In clinical practice at our institution, ejection fraction < 50% is not used as an absolute contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%, potentially cardiotoxic therapy is most often discontinued or omitted. Radionuclide evidence of cardiac reserve may account for decisions to continue cardiotoxic agents despite ejection fractions < 50% in the majority of patients. Further study will be needed to establish standard criteria. Reserve function, as measured by the change in ejection fraction from rest to stress may be an important parameter used by oncologists to help select patients for continued therapy in spite of a reduced ejection fraction. Our results argue that use of fixed criteria may be too restrictive.